The Effect of Imatinib (Glivec®) on Scleroderma and Normal Dermal Fibroblasts: A Preclinical Study
| Autor: | Thierry Schaeverbeke, F.X. Mahon, Catherine Pain, Sébastien Lepreux, J.M. Pasquet, Muriel Cario-André, Hamid Reza Rezvani, A. Soria, Alain Taïeb |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Adolescent medicine.drug_class Blotting Western Dermatology Piperazines Tyrosine-kinase inhibitor Scleroderma Receptor Platelet-Derived Growth Factor beta Dermal fibroblast Growth factor receptor Dermis Humans Medicine skin and connective tissue diseases Protein Kinase Inhibitors neoplasms Cells Cultured Aged Cell Proliferation Skin Aged 80 and over Scleroderma Systemic integumentary system biology business.industry Imatinib Fibroblasts Middle Aged Protein-Tyrosine Kinases medicine.disease Immunohistochemistry Pyrimidines Treatment Outcome medicine.anatomical_structure Benzamides embryonic structures Imatinib Mesylate cardiovascular system biology.protein Female business Platelet-derived growth factor receptor medicine.drug |
| Zdroj: | Dermatology. 216:109-117 |
| ISSN: | 1421-9832 1018-8665 |
| DOI: | 10.1159/000111507 |
| Popis: | Background: Scleroderma skin overexpresses the platelet-derived growth factor receptor β-subunit (PDGFR-β) in dermal vessels and PDGFR-β messenger RNA in cultured fibroblasts. Moreover, increased levels of PDGF and stimulatory autoantibodies to PDGFR have been identified in the serum of scleroderma patients. Objective: Imatinib being an inhibitor of tyrosine kinase receptors such as PDGFR, its effect on scleroderma fibroblasts was evaluated in vitro as a preclinical therapeutic step. Methods: The effect of imatinib on fibroblasts grown from normal or involved/uninvolved scleroderma skin was studied by Western blot and the methyltetrazolium test. The pattern of distribution of PDGFR-β in scleroderma versus normal skin was studied by immunohistochemistry. Results: In vitro, imatinib inhibited the proliferation of normal dermal and scleroderma fibroblasts at least partly via the inhibition of the phosphorylation of PDGFR. PDGFR-β was expressed in the epidermis and adnexae in 5 lesional scleroderma biopsies and not in controls. Conclusion: This study suggests that imatinib can serve as therapy to limit dermal fibroblast proliferation in scleroderma. |
| Databáze: | OpenAIRE |
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